Case report: Conversion therapy for advanced intrahepatic cholangiocarcinoma using PD-1 inhibitor plus S-1 and nab-paclitaxel

Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant hepatobiliary tumor with a high rate of advanced disease at initial presentation. Conversion into resectable iCCA is important for improving the prognosis. Immunotherapy-based regimens are being increasingly used for treating advanced iCCA in recent years. However, the use of combined chemotherapy and immunotherapy for conversion has rarely been reported. The aim of this report was to present the outcomes of a 52-year-old female patient with IIIB iCCA. The patient was treated with a programmed cell death protein-1 inhibitor plus S-1 and nab-paclitaxel. The postoperative histopathological results indicated pathologic complete response after six cycles of systematic treatment. The patient is currently disease-free for one year

Using T-cell repertoire profiles as predictor in a primary mucosal melanoma

Dear Editor, Primary mucosal melanoma is a rare subtype of melanoma that carries poor prognosis. Traditional treatment options of mucosal melanoma are surgery, radiation, and chemotherapy; but the overall survival remains low.1 Cytotoxic T‐lymphocyte associated protein 4 (CLTA‐4) and programmed cell death protein 1 (PD‐1), both inhibitory immune checkpoints commonly seen on activated T cells, have been found to be promising targets for treatment of advanced cancers.2 However, the efficacy and response to immunotherapy in mucosal melanoma remains unknown. Herein, we report a case involving a patient, who was a 70‐year‐old male and referred to Taipei Medical University Hospital with confirmed diagnosis of mucosa melanoma over hard plate of mouth. The patient was admitted and subjected to anti‐PD‐1 immunotherapy (pembrolizumab 200 mg every 3 weeks) (Figure 1A). Serial imaging of primary malignant melanoma of the hard palate showed that the tumor size gradually decreased after treatment with pembrolizumab, suggesting partial response/stable disease secondary to continuous immunotherapy (Figure 1B). However, after seventh cycle of treatment, magnetic resonance imaging (MRI) revealed enlarged previous known metastatic lesions and new tumor nodules in brain (Figure 1B). The patient received stereotactic radiation therapy before treatment cycle 14 (Figure 1A). Although the primary metastatic brain lesions were smaller and stationary after radiotherapy, the following brain MRI displayed several hyperdensity masses in the right frontal lobe with perifocal edema and mild mass effect (Figure 1B). Subsequently, patient suffered from infection and respiratory distress and died 2 months after 17th cycle of pembrolizumab therapy

Using T-cell repertoire profiles as predictor in a primary mucosal melanoma

Dear Editor, Primary mucosal melanoma is a rare subtype of melanoma that carries poor prognosis. Traditional treatment options of mucosal melanoma are surgery, radiation, and chemotherapy; but the overall survival remains low.1 Cytotoxic T‐lymphocyte associated protein 4 (CLTA‐4) and programmed cell death protein 1 (PD‐1), both inhibitory immune checkpoints commonly seen on activated T cells, have been found to be promising targets for treatment of advanced cancers.2 However, the efficacy and response to immunotherapy in mucosal melanoma remains unknown. Herein, we report a case involving a patient, who was a 70‐year‐old male and referred to Taipei Medical University Hospital with confirmed diagnosis of mucosa melanoma over hard plate of mouth. The patient was admitted and subjected to anti‐PD‐1 immunotherapy (pembrolizumab 200 mg every 3 weeks) (Figure 1A). Serial imaging of primary malignant melanoma of the hard palate showed that the tumor size gradually decreased after treatment with pembrolizumab, suggesting partial response/stable disease secondary to continuous immunotherapy (Figure 1B). However, after seventh cycle of treatment, magnetic resonance imaging (MRI) revealed enlarged previous known metastatic lesions and new tumor nodules in brain (Figure 1B). The patient received stereotactic radiation therapy before treatment cycle 14 (Figure 1A). Although the primary metastatic brain lesions were smaller and stationary after radiotherapy, the following brain MRI displayed several hyperdensity masses in the right frontal lobe with perifocal edema and mild mass effect (Figure 1B). Subsequently, patient suffered from infection and respiratory distress and died 2 months after 17th cycle of pembrolizumab therapy

Comparative Proteomic Approach Identifies Pkm2 and Cofilin-1 as Potential Diagnostic, Prognostic and Therapeutic Targets for Pulmonary Adenocarcinoma

Lung cancer is the leading cause of cancer-related death in the world. Non-small cell lung carcinomas (Non-SCLC) account for almost 80% of lung cancers, of which 40% were adenocarcinomas. For a better understanding of the molecular mechanisms behind the development and progression of lung cancer, particularly lung adenocarcinoma, we have used proteomics technology to search for candidate prognostic and therapeutic targets in pulmonary adenocarcinoma. The protein profile changes between human pulmonary adenocarcinoma tissue and paired surrounding normal tissue were analyzed using two-dimensional polyacrylamide gel electrophoresis (2-DE) based approach. Differentially expressed protein-spots were identified with ESI-Q-TOF MS/MS instruments. As a result, thirty two differentially expressed proteins (over 2-fold, p<0.05) were identified in pulmonary adenocarcinoma compared to normal tissues. Among them, two proteins (PKM2 and cofilin-1), significantly up-regulated in adenocarcinoma, were selected for detailed analysis. Immunohistochemical examination indicated that enhanced expression of PKM2 and cofilin-1 were correlated with the severity of epithelial dysplasia, as well as a relatively poor prognosis. Knockdown of PKM2 expression by RNA interference led to a significant suppression of cell growth and induction of apoptosis in pulmonary adenocarcinoma SPC-A1 cells in vitro, and tumor growth inhibition in vivo xenograft model (P<0.05). In addition, the shRNA expressing plasmid targeting cofilin-1 significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. While additional works are needed to elucidate the biological significance and molecular mechanisms of these altered proteins identified in this study, PKM2 and cofilin-1 may serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets for pulmonary adenocarcinoma

Letter of Intent: Jinping Neutrino Experiment

Jinping Neutrino Experiment (Jinping) is proposed to significantly improve measurements on solar neutrinos and geoneutrinos in China Jinping Laboratory - a lab with a number of unparalleled features, thickest overburden, lowest reactor neutrino background, etc., which identify it as the world-best low-energy neutrino laboratory. The proposed experiment will have target mass of 4 kilotons of liquid scintillator or water-based liquid scintillator, with a fiducial mass of 2 kilotons for neutrino-electron scattering events and 3 kilotons for inverse-beta interaction events. A number of initial sensitivities studies have been carried out, including on the transition phase for the solar neutrinos oscillation from the vacuum to the matter effect, the discovery of solar neutrinos from the carbon-nitrogen-oxygen (CNO) cycle, the resolution of the high and low metallicity hypotheses, and the unambiguous separation on U and Th cascade decays from the dominant crustal anti-electron neutrinos in China.Comment: Proposal for the Jinping Neutrino Experimen

Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway

Background: Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long noncoding RNA, is significantly highly expressed and associated with metastasis and poor prognosis in many cancers, including nasopharyngeal carcinoma (NPC). In this study, we aim to identify the role of AFAP1-AS1 acting as an oncogenic lncRNA to promote NPC metastasis. Methods: The role of AFAP1-AS1, miR-423-5p, and FOSL2 in NPC metastasis was investigated in vitro and in vivo. Bioinformatics analysis and luciferase activity assays were used to identify the interaction between AFAP1-AS1, miR-423- 5p, and FOSL2. Additionally, real-time PCR and western blotting were used to assess the function of AFAP1-AS1 acting as an oncogenic lncRNA to promote NPC progression by regulating miR-423-5p and the downstream Rho/Rac pathway. Results: In this study, we determined that AFAP1-AS1 functions as a competing endogenous RNA in NPC to regulate the Rho/Rac pathway through miR-423-5p. These interactions can mediate the expression of RAB11B, LASP1, and FOSL2 and accelerate cell migration and invasion via the Rho/Rac signaling pathway or FOSL2. AFAP1-AS1 and FOSL2 could competitively bind with miR-423-5p to regulate several molecules, including RAB11B and LASP1 of the Rho/Rac signaling pathway. AFAP1-AS1 can also regulate the expression of LASP1, which was transcriptionally regulated by FOSL2, resulting in increased migration and invasion of NPC cells via the Rho/Rac signaling pathway. Conclusions: The observations in this study identify an important role for AFAP1-AS1 as a competing endogenous RNA (ceRNA) in NPC pathogenesis and indicate that it may serve as a potential target for cancer diagnosis and treatment